The present invention relates to a system and method of assessing the medical risk of a given outcome for a given patient, and, in particular to prenatal risk evaluation.
Maternal serum alpha-fetoprotein (MSAFP) screening for the detection of fetal abnormalities and abnormal pregnancies has been used for over twenty years by obstetricians and geneticists. AFP screening is particularly applicable to women who conceive over the age of 35, a time point at which the incidence of abnormal pregnancies and fetal defects increases dramatically. An elevation in MSAFP is associated with a number of fetal anomalies, including open neural tube defects such as spina bifida and anencephaly, congenital nephrosis, and gastrointestinal tract abnormalities.
In 1984, a low maternal serum AFP level was reported to be predictive of fetal chromosomal anomalies as well, including the risk of Down's Syndrome. Since a low maternal serum AFP value is effective in identifying only 20% of Down's Syndrome affected cases, additional markers were sought which could add to the predictive value of this test. Maternal serum human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) levels have both been described as providing additional information, useful for estimating the probability of fetal Down's Syndrome.
The evidence that hCG measurements provide an additional prognostic marker of Down's Syndrome risk in afflicted pregnancies is considerably stronger than the contribution of unconjugated estriol (uE3). However, many laboratories have incorporated all three tests, AFP, hCG, and uE3, for prenatal screening programs targeted at high risk pregnancy populations.
In the course of attempting to optimize the use of MSAFP testing, a number of variables have been identified which can influence the interpretation of AFP results. Besides developing normative data matched to the gestational period, since AFP appears in the maternal circulation normally with increasing concentration as pregnancy develops, maternal weight, race and diabetic status have also been shown to be confounding variables which can alter the reference base by which one judges the result to be normal or abnormal. This has necessitated the establishment of median values for MSAFP from a normal, healthy pregnancy population between 14 and 20 weeks of gestation (EGA). Also, the normal variability of MSAFP at each week of gestation has been evaluated, and found to span a range of 2.5 multiples of the median (MoM). Once the MoM value from the MSAFP is calculated, the influence of maternal weight, race, and diabetic status on the MoM calculation is determined using correction factors established from the literature. The final adjusted MoM value is interpreted by comparison to the normal database. The clinical interpretation of these markers is dependent on their relationship to each other, as well as the specimen source and EGA.